In this study, we are proposing to assess comparative efficacy of a TCA (nortriptyline) and an MAOI (phenelzine) over placebo in three groups (50 patients per group) of carefully screened depressed geriatric patients by optimizing treatment. We are also going to examine the nature of the relationship, if any, between plasma steady state nortriptyline (NT) levels, platelet MAO inhibition, and any occurring undesirable effects for optimal monitoring the dosage of these medications. For this, 150 geriatric patients suffering from major depressive illness, primary, unipolar, will be randomly assigned to NT, phenelzine or placebo in double-blind design following a 7 day placebo-washout period. Dosage will be adjusted according to steady state plasma NT levels (50-180 ng/ml) or platelet MAO inhibition (equal or above 80%). Duration of treatment period will be 7 weeks. In addition, patients will undergo an extensive psychiatric, psychometric and neuroradiological evaluations at different times throughout the study. It is hoped to generate more specific psychopharmacological strategies to treat depression in the elderly as well as to increase our understanding of the nature of depressive illness in the elderly.